The operation of gyrotron-based dynamic nuclear polarization/nuclear magnetic resonance (DNP/NMR) spectrometers is proposed. Two systems are envisioned. The first instrument, now under construction, will operate at a magnetic field of 9 T (250 GHz for g=2 electrons and 380 MHz for 1H NMR). The second instrument will be a 494 GHz gyrotron that will be integrated into a new 750 MHz NMR wide-bore spectrometer to be located at MIT. The rationale for the continued development of these instruments is threefold: 1. Using a 5 T DNP/NMR gyrotron-based spectrometer, we have demonstrated DNP enhanced magic angle spectra (MAS) of the protein T4 lysozyme. At ~55k we have achieved enhancements of ~50 in 15/N spectra. This dynamic increase in sensitivity permits structure/function studies of macromolecules with molecular weights of 10/5 or greater. Resolution and sensitivity will be further improved at higher fields. 2. At 140 GHz the resolution of EPR spectra due to g value dispersion increases dramatically. This has permitted us to record a number of spectra of paramagnetic proteins for example, photosystem I and II, ribonucleotide reductase, galactose oxidase, etc. which provide answers to important biochemical problems not available from lower field spectra. We anticipate similar informative results at 25 GHz. 3. The critical factor that has impeded the extension of DNP and pulsed EPR research to higher frequencies has been the lack of microwave source with adequate power. We have recently overcome this problem with the successful development of a 250 GHz CW gyrotron that has operated reliably at powers up to 25 watts. We therefore propose the following: DNP/NMR 380 MHz Spectrometer: We will complete the construction of a 380 MHz spectrometer and begin DNP and EPR studies. This spectrometer will utilize a 125 mm bore, 9.0T NMR magnet with a +/- 1 T sweepable B/0 field, and DNP/MAS probes. A quasi-optical transmission line will be used to efficiently couple the microwave power into the sample. Both CW and pulsed EPR studies will be conducted. DNP/NMR 750 MHz Spectrometer: Once the viability of DNP at 380 MHz is demonstrated, we will extend this technique to 750 MHz on a new spectrometer at MIT. This will require the construction of a 500 GHz harmonic gyrotron oscillator and the integration of this source into the NMR spectrometer. Advanced Gyrotron Technology: We will investigate 250 GHz gyro- amplifiers, which could provide both tunability (0.5-1.0% bandwidth) and advanced pulse formats for EPR studies. We will also extend gyrotron oscillators to 600-800 GHz. Such gyrotrons could be used with future 0.9- 1.2 GHz NMR spectrometers.